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<title>New Diabetes Drug Faces a Critical Review Before an F.D.A. Advisory Panel</title>
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New <a href="http://health.nytimes.com/health/guides/disease/diabetes/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Diabetes." class="meta-classifier">diabetes</a> drugs are being developed that reduce blood sugar in a straightforward way — by causing it to be excreted in the urine.        </p>      <p>
On Tuesday, a committee that advises the <a href="http://topics.nytimes.com/top/reference/timestopics/organizations/f/food_and_drug_administration/index.html?inline=nyt-org" title="More articles about the U.S. Food And Drug Administration." class="meta-org">Food and Drug Administration</a> is to consider whether the first of those drugs can overcome safety concerns and reach the market.        </p><p>
The outcome of the F.D.A. review is far from certain. The drug, dapagliflozin, might raise the risk of breast and <a href="http://health.nytimes.com/health/guides/disease/bladder-cancer/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Bladder cancer." class="meta-classifier">bladder cancer</a>, liver damage and infections of the genitals and urinary tract, according to an F.D.A. examination of the data posted on the agency’s Web site on Friday.        </p><p>
<a href="http://topics.nytimes.com/top/news/business/companies/bristol_myers_squibb_company/index.html?inline=nyt-org" title="More information about Bristol Myers Squibb Company" class="meta-org">Bristol-Myers Squibb</a> and AstraZeneca, the co-developers of dapagliflozin, are in the lead to bring these drugs, so-called SGLT2 inhibitors, to market. Others developing such drugs include Johnson &amp; Johnson; the team of Eli Lilly and Boehringer Ingelheim; Lexicon Pharmaceuticals; Isis Pharmaceuticals; and several Japanese companies including Astellas Pharma, the Chugai Pharmaceutical Company and the Taisho Pharmaceutical Company.        </p><p>
Currently, only a tiny amount of glucose that is filtered by the kidneys is excreted in the urine; the rest is returned to the bloodstream. This mechanism apparently evolved to help the body preserve a vital source of energy.        </p><p>
The job of returning glucose to the bloodstream is performed mainly by a protein called the sodium glucose co-transporter 2. By inhibiting SGLT2, the drugs cause a substantial increase in the amount of glucose that flows out in the urine.        </p><p>
At least in principle, this does not appear to be dangerous. There is a rare genetic disease in which people do not have functioning SGLT2. They have very high sugar levels in their urine but appear otherwise to be generally healthy.        </p><p>
In clinical trials, dapagliflozin, a once-a-day pill, was about as effective as other types of diabetes drugs in lowering blood sugar. According to the F.D.A., however, the drug does not work in patients with moderate to severe kidney impairment.        </p><p>
Experts say that SGLT2 inhibitors would be a useful addition because many diabetics go through various drugs, often more than one at a time, to try to control their blood sugar.        </p><p>
“It’s not a must-have, but it’s a nice thing,” said Dr. Jay S. Skyler, deputy director of the Diabetes Research Institute at the University of Miami. “I’d like to have it in my toolbox.”        </p><p>
A potential advantage of these drugs is that their mechanism of action is independent of insulin, making it potentially easy to combine SGLT2 inhibitors with other drugs. Many other diabetes drugs work either by providing the body with insulin, inducing the pancreas to secrete more insulin or making the body more sensitive to insulin.        </p><p>
Moreover, because so many <a href="http://health.nytimes.com/health/guides/nutrition/diet-calories/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Diet - calories." class="meta-classifier">calories</a> are now flowing out in the urine, the SGLT2 inhibitors help people lose a little weight. That could be of some benefit because many people with diabetes are overweight and because some other diabetes drugs can cause weight gain.        </p><p>
In clinical trials, patients receiving dapagliflozin lost an average of about five pounds more than those getting a placebo after six months. They also experienced a slight reduction in <a href="http://health.nytimes.com/health/guides/test/blood-pressure/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Blood Pressure." class="meta-classifier">blood pressure</a>.        </p><p>
One drawback, however, is that the extra sugar in the urine makes the urinary tract and genitals more hospitable to micro-organisms, leading to an increase in infections.        </p><p>
What seemed to concern the F.D.A. reviewers more than these infections was a possible increased risk of breast and bladder cancers.        </p><p>
Nine women, or 0.4 percent of those who took the drug, got <a href="http://health.nytimes.com/health/guides/disease/breast-cancer/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Breast cancer." class="meta-classifier">breast cancer</a> compared with one woman, or 0.09 percent, of those in the control group, according to AstraZeneca and Bristol-Myers. For bladder cancer, the rate was nine cases, or 0.3 percent, for those taking the drug compared with one case, or 0.05 percent, for those in the control group.        </p><p>
The companies argue that when all types of <a href="http://health.nytimes.com/health/guides/disease/cancer/overview.html?inline=nyt-classifier" title="In-depth reference and news articles about Cancer." class="meta-classifier">cancer</a>, not just breast and bladder cancer, are considered, there is no increased risk for those taking dapagliflozin. They also say that some of the cancers were diagnosed so soon after the start of the trial that they were unlikely to be linked to the drug.        </p><p>
“Based on a thorough nonclinical and clinical assessment, the data do not suggest that dapagliflozin is associated with a risk for either of these cancers,” the companies wrote in their own briefing document, adding, however, that data was limited.        </p>
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